A heart valve is designed to provide precise mechanical function in an atmosphere of constant high pressure and movement during the entire life of an individual. On those occasions when disease of a valve supervenes, the morbidity and mortality is high even though modern cardiac surgery and replacement of heart valves with prostheses may provide some relief. The major structural component responsible for strength and resiliency of heart valve is collagen. We propose to investigate heart valve collagen using modern biochemical techniques. Heart valve collagen will be solubilized with pepsin and its component chains purified by ion exchange and molecular sieve chromatography. The isolated purified heart valve collagen chains will be characterized by amino acid analysis and assays for hydroxylysine glycosides, carbohydrate, uronic acid, and amino sugars. The molecular species of collagen of each chain will be determined following isolation, purification and characterization of the corresponding cyanogen bromide peptides. Pepsin insoluble collagen will be characterized following cleavage by cyanogen bromide. The resulting cyanogen bromide peptides will be isolated by ion exchange and molecular sieve chromatography and characterized for amino acid composition and size. Cross-linking in heart valve collagen will be analyzed directly on whole heart valve, on pepsin insoluble heart valve and on pepsin soluble isolated heart valve collagen chains. Pathologic human heart valves removed during surgery or collected at autopsy will be characterized for abnormalities in collagen utilizing microtechniques and fibroblast culture. Knowledge of the nature of heart valve collagen and its alterations in disease provide a framework to design better therapeutic and preventative approaches.